Studies on treatment of diabetes using materials having glucose-responsive characteristics have been conducted. Up to date, polymeric composites using phenylboronic acid have been widely used to treat diabetes, and methods using the composites as drug delivery systems have been developed. Also, studies on cancer treatment using biocompatible polymer nanoparticles have been actively conducted. However, most studies have side effects of destroying normal cells as well as cancer cells.
Research on cancer-specific delivery of contrast agents and anticancer agents having potential toxicity using biocompatible materials has been actively conducted. In recent years, the research paradigm for ‘theragnosis’ has come into the spotlight as one of the fusion techniques enabling simultaneous diagnosis and therapy [Ryu J et al., “Tumor-targeting multi-functional nanoparticles for theragnosis: New paradigm for cancer therapy,” Advanced Drug Delivery Reviews 64: 1447-1458 183-192(Jul. 4, 2012)]. Cancer cells have a Warburg effect in which the cancer cells inefficiently produce energy, compared to the normal cells. This abnormal glycolysis results in the uptake of a high concentration of glucose into the cancer cells [Reuben J S, “Glucose metabolism and cancer”, Current Opinion in Cell Biology 18: 598-608 (Oct. 12, 2006); Robert A G et al., “Why do cancer have high aerobic glycolysis”, Nature Review 4: 891-899 (November 2004)]. Examples of diagnosis of cancers using the unique biological mechanism of such cancer cells have been reported. However, no application to simultaneous cancer diagnosis and therapy through the regulation of cell metabolism has been reported yet.
On the other hand, it has been reported that hydrophobic phenylalanine-based compounds specifically bind to glucose to lose their hydrophobic property [Shull B et al., “P-Boronophenylalanine complexes with fructose and related carbohydrates and polyols”, U.S. Pat. No. 6,169,076 B1 (Jan. 2, 2001)]. There are reports on the application of this phenomenon to treatment of diabetes [Kataoka, K, et al. “Totally synthetic polymer gels responding to external glucose concentration: Their preparation and application to on-off regulation of insulin release.” Journal of the American Chemical Society 120: 12694-12695 (November 1998)]. However, no application of such a phenomenon to simultaneous cancer diagnosis and therapy has been reported yet.
As the prior art for diagnosis and treatment of diseases, target-directed probes, contrast agents, and biocompatible delivery systems including a therapeutic agent have been widely used. In particular, many polymer nanoparticles that can be used to simultaneously diagnose and treat cancer have been developed. However, most of the contrast agents used for simultaneous diagnosis and treatment of cancer have potential toxicity problems, which have been raised so far, such as kidney toxicity and exposure to radiation. Also, the uncontrollable risk caused by non-specific delivery of the anticancer agents has become a leading cause of limiting the therapy using the anticancer agents to ancillary therapeutic methods in the field of clinical trials.
Throughout this application, many publications and patents are referenced and the citations thereof are provided in parentheses. The disclosures of these publications and patents are hereby incorporated by reference in their entities into this application in order to fully describe the present invention and the state of the art to which the present invention pertains.